O-chloroalkyl o-alkylmercaptoalkyl and o-chloroalkyl s-alkylmercaptoalkyl esters of alkyl phosphonic acids



United States Patent 0 8 Claims. 51. 26tl-461) The present invention relates to and has as its objects new and useful phosphonic acid derivatives and processes for the production thereof. Generally the new inventive compounds may be represented by the following formula fi/O-allcCl R-P X-R in which R stands for an optionally substituted preferably lower alkyl radical and all; denotes an alkylene radical optionally substituted, and wherein R stands for an aliphatic, cycloaliphatic, araliphatic, aromatic or heterocychc radical, which possibly may be substituted by convenient substituents, X and Y stand for oxygen or sulphur.

In accordance with the present invention it has been found that by reaction of the highly reactive alkyl-phosphonous acid-O-chloroalkyl ester mono-chlorides of the general formula O-alk-C] with optionally substituted alcohols, phenols or aliphatic, cycloaliphatic, aromatic or heterocyclic mercaptans in the presence of a suitable acid-binding agent there are obtained the hitherto unknown alkylphosphonous or alkylthiophosphonous acidO-chloroalkyl-esters of the following constitution:

O-alk-Cl RP/ The last-mentioned derivatives of trivalent phosphorus can then themselves be converted according to methods known in principle by treatment with hydrogen peroxide, elementary sulphur or sulphur-yielding compounds into the corresponding alkyl-phosphonic or alkyl-thiophosphonic-O-chloroalkyl-acid esters of the general formula:

The inventive reaction may be explained in more detail by the following equation:

In the above formulae the symbols R, R alk, X and Y have the same significance as given above.

When carrying out the reaction according to the invention is is not necessary to isolate the alkylphosphonous acid-0,0- or -O,S-diesters produced in the first stage of reaction in substance; instead the reaction products of alkylphosphonous acid-Ochloralkyl ester monochiorides with alcohols, phenols or mercaptans are with advantage 3,187,35 Patented June 1, .1955

ice

immediately further reacted as a single operation with hydrogen peroxide or sulphur to give the corresponding phosphonic acid-0,0- or -O,S-diesters.

The alkylphosphonous acid-O-chloralkyl ester monochlorides can be produced by the reaction of alkylphosphonous acid dichlorides in suitable solvents and in the presence of acid-binding agents with alkylene oxides as it is already been known from the literature [cf. S. Z. Iwin, K. W. Karawanow, J. allgem. Chem. (Russ), volume 29, page 3456 (1959)].

According to the data given by the aforesaid Russian authors the reaction of, for example, ethylene oxide with alkylphosphonous acid dichlorides leads to the successive exchange of the two chlorine atoms for the ffi-chloroethoxy radical, the following compounds thus being obtained:

The alkylphosphonous acid-O-chloroalkyl ester chlorides required as starting materials for the process according to the invention can also be produced, in addition to the method already described, by reacting alkylene chlorohydrins with the said phosphonous acid derivatives.

By way of example of alkylphosphonous acid-O-chloroalkyl ester chlorides which can be employed according to the invention there may be mentioned the methyl-, ethyl-, n-propyl-, isopropyl-, n-bntyl-, iso-butyl-, tert.-butyl-, amylor hexyl-phosphonous acid-O-chloroethyl-, -propylor -butyl-ester chlorides.

Moreover the new process can .be applied to practically all alcohols, phenols or rnercaptans. By Way of alcohols use can be made, e.g. of hexanol, cyclohexanol, octylor dodecyl alcohol, the corresponding mercaptans as Well as of lower aliphatic alcohols or mercaptans which may be optionally substituted by halogen atoms, cyano, amino, alkylor dialkylarnino hydroxy, alkoxy, carbalkoxy, alkylmercapto groups and the like. As phenols or thiophenols, consideration can be given to, inter alia, (thio)-phenol, (thio)-cresols, chloro-(thio)-phenols, diand tri-chloro- (thio) -phenols, alkyl- (thio )-phenols, allcyl-chloro- (thio) phenols, alkoxyor alkylmercapto-(thio)-phenols, alkoxyor alkylmercapto-alkyl-(thio)-phenols or Intro-(thio)- phenols for the use as starting materials in the process according to the invention.

As already mentioned the inventive reaction of the alkyl phosphonous acid-O-chloroalkyl ester chlorides with the aforesaid alcohols, phenols or mercaptans preferably is carried out in the presence of acid binding agents; among these tertiary amines e.g. pyridine, triethylamine, or dimethylaniline have been found to be particularly useful.

Moreover in order to obtain especially good yields and pure products, it is expedient to carry out the reaction ac cording to the invention at slightly elevated temperatures and, moreover, to afterheat the reaction products for some time in order to complete the reaction. Furthermore the use of inert solvents has proved to be advantageous. As solvents low-boiling hydrocarbons such as petroleum ether, ligroin, benzene or toluene have been found to beespecially suitable.

In addition for the purpose of avoiding any interference by side reactions it is further advantageous to carry out the inventive reactions in an atmosphere of a protective gas (conducting a stream of an inert gas e.g. nitrogen or argon through the reaction mixture).

The phosphonic acid esters obtainable according to the activity.

liquids which can be distilled under a high vacuum without decomposition. They are. characterized by excellent insecticidal properties. The inventive compounds especially distinguish themselves by an outstanding contact in secticidal activity, against spider mites and aphids, but at the same time also against eating insects '(e.g. caterpillars)-and possess moreover an ovicidal and systemic f Therefore, the compounds obtainable'according to'the' process of the invention are intended to be used as pest control agents, chiefly for plant protection. The products are applied for this specified purpose in the manner cus tomary for phosphorus-containing plant protectives or pest control agents, i.e. preferably in a concentration from about 0.00001% to about 1% and in combination with suitable solider liquid extenders or diluents.

Examples of such solid carriers are talc, chalk, be'ntonite, clay and the like, as liquid carriers there may be mentioned water (if necessary with commercial emulsifiers), alcohols, especially lower alcohols such as methanol or ethanol, ketones, especially lower ketones such as acetone or methyl ethyl ketone, liquid hydrocarbons and the like. The new compounds may furthermore be used in combination with each other or with known. insecticides, fertilizers etc.

As examples for the special utility the compounds of the following formula have been tested against aphids and spider mites. Aqueous dilutions of these compounds have been prepared by admixing them with the same amount of dimethyl formamide as an auxiliary solvent adding, thereto 20% by weight referred to active ingredient of a commercial emulsifier consisting of a benzyl hydroxyl polyglycol ether containing about to glycol residues, and diluting at last this premixture with water to the desired concentrationindicated in the following paragraphs:

. The tests have been carried out as follows:

(a) Against aphids (contact-insecticidal action) of the type Doralis fabae. Heavily infested bean plants (Vicia faba) have been sprayed drip wet with solutions as prepared above. The eifect has been determined by evaluation after 24 hours by counting the dead pests either on the surface of the soil or still remaining on the plants. The following results have been obtained:

Aqueous concentration (in Killing rate I (b) Against'spider mites (contact-insecticidal action). Bean plants (Phaseolus vulggris) of about 15 inches height are sprayed drip wet with solutions prepared as indicated above. The bean plants have been infested heavi- 1y with the two-spotted spider (species Tetranychus telarius). Evaluation has been carried out after 24 hours, 48 hours, 8 days. The following results have been obtained:

Aqueous eoneentration (in Killing rate Compound percent active (in percent) ingredient} water) The following examples are given for the purpose of illustrating the invention, without however, limiting it thereto. 4

Example 1 0.0Hz-CH2.C1

O 0.CH2-CH2.C1 ll 2 5-1 (b) To a solution of 50 g. of pyridine and61'g. of 5- ethyl-mercapto-ethyl' mercaptan in 400cc. of benzene there are added dropwise at 30 to 40 C. while stirring 88 g. (0.5 mol) of ethyl-phosphonous acid-O-fi-chloroethyl ester. chloride, the mixture is then further stirred at 30-35 C. for one hour and subsequently treated with 50 g. of 37% hydrogen peroxide while stirring is con tinued. The reaction mixture is then afterstirred for a further hour, washed with a 3% sodium bicarbonate solution, dried over sodium sulphate and finallyfractionated by distillation. In this way 44 g. (32% of the theoretical amount) of ethyl-thiolphosphonic-acid-Q-pchloro'ethyl-S-(fl-ethyl-mercapto-ethyl) ester of BF. 106 'C./0.0l mm. Hg are obtained.

The mean toxicity 'of this compound'on rats per os is 3 mg. per kg. of animal. Spider mites are destroyed to 100% with 0.01% solutions of the ester, whilst 0.001% solutions destroy aphids to By exactly the same way there may be obtained the following compounds: 7

" s-on oHrs-czm s-om-cm-om-s ozm 0.0'H..0H..s c2115 50 g. of pyridine and 3 g. of fl-ethylmercapto ethanol are dissolved in 400 cc. of benzene, 88 g. (0.5 mol) of ethyl-phosphonous acid-O-fi-chloroethyl ester chloride are added dropwise to this solution at 30-40 C. while stirring, the mixture is subsequently further stirred for one hour and then treated with 16 g. of finely powdered sul phur, whereupon the temperature of the reaction mixture spontaneously rises to 50 C. To complete the reaction, the mixture is further heated to 75 to 80 C. for one hour and then worked up as described in Example 1(b). 81 g. (59% of the theoretical amount) of ethyl-thionophosphonic acid-O-fi-chloroethyl-O-(fi-ethylmercapto-ethyl) ester of B.P. 98 C./0.0l mm. Hg are thus obtained.

On rats per es the compound shows a mean toxicity (D11 of 5 mg. per kg. of animal. Spider mites are destroyed to 100% by 0.001% solutions and aphids by 0.01% solutions of the ester. The compound hasmoreover an ovicidal activity and shows good systemic properties.

In the same manner as described above the following compounds may be obtained:

To a solution of 50 g. of pyridine and 53 g. of B-ethylmercapto-ethanol in 400 cc. of benzene there is added dropwise at 30 C. while conducting nitrogen through the reaction mixture 88 g. (0.5 mol) of ethyl-phosphonous acid-B-chloroethyl ester chloride, the mixture is subsequently heated to 40 C. for one hour and then treated with 50 g. of 37% hydrogen peroxide while stirring is continued. After termination of the addition, the mixture is heated to 35 C. for a further hour and then worked up as described in Example 1(b). .In this way, 39 g. (30% of the theoretical amount) of ethyl-phosphonic aeid-O-B-chloroethyhO-(,B-ethylmercapto-ethyl) ester of B.P. 96 C./0.01 mm. Hg are obtained in form of a water-soluble oil.

Administered per os the mean toxicity of the compound is 375 mg. per kg. of rat.

By the same way there may be produced the following compounds:

Example 4 50 g. of pyridine and 61 g. of p-ethylmercapto ethylmercaptan are dissolved in 400 cc. of benzene. To the resultant solution, 88 g. (0.5 mol) of ethyl-phosphonous acid-,B-chlorethyl ester chloride are added at 40 C. while stirring, the mixture is heated at 40 C. for one hour and 16 g. of finely powdered sulphur are then added. Subsequently the reaction mixture is heated to C. for a further hour and then worked up as described in Example 1(b). 82 g. (56% of the theoretical amount) of ethylthionothiolphosphonic acidO-fi-chloroethyl S (fl-ethylmerca'pto-ethyl) ester of RP. 103 C./0.01 mm. Hg are thus obtained. Mean toxicity of the compound on rats per 0s: 5 mg. per kg. of animal. Spider mites are destroyed to by 0.001% solutions, eating insects (caterpillars) by 0.1% solutions. The compound has moreover an ovicidal activity and also shows systemic action.

Under the same conditions there may be obtained the compounds of the following formulae:

, s o-om-crn-or CgI-Ial r s-cn-oH,-soH3 HI 7. I claim: 1 V I 1. A compound of the formula i I X O-alk cl 3' i Y-alk-SR wherein R and R each stand for lower 'alkyl having up to 4 carbon atoms; a lk stands for lower al'kylene having up to 4 carbon atoms; and X and Y eachstand for a member selected from the grou-p consisting of oxygen and sulfur, with the proviso that when Y stands for oxygen, X stands for oxygen.

2. A compound of claim -1 wherein X and Y are each oxygen. a I

3. A compound of claim 1 wherein X and Y are each sulfur.

4; A compound of claim 1 wherein X is oxygen and Y is sulfur. V

5. The compound of the following formula 0 o0H,-0H5-CI CE5--P s-om-cnrsczm 6 The compound of the following formula o 0-CHCH,C1

CIHBP OCHzC z'S z 5 8 7. The compound of thefollowing formula S O--CH'g-'-'CHFC1 C1H5-IILL/ I '0=-0H, cH, -sO,H5

8. The compound of'the following formula I s O-CH CH,C1

c,H5P V.

scH,-oi1,-so,n, References Cited By the Examiner UNITED sTATEs- PATENTS 2,881,201 4/59 Schrader 260--46 1.110 2,895,983 7/59 Assefi 260461.110 2,907,787 10/59 IH-oifmann" e181- 260461.110, 2,957,019 10/60 McCall et al- 260461.112 2,988,748 '5/6=1 'Schlor 260461.110 3,020,305 .2/62 :Chupp ,2e0 461.112 FOREIGN PATENTS,

218,030 11/61 Austria. 7 I 7 OTHER RE E ENCES 7 Kabachnik et'aL: Chem; A-b.st.,","vol. .54, col. 8594 (1960). V I

Aaron et al.: I. Am. Chem, Soc.,' vol. 80, pp. 456458 Volkova; Vaprosy Med. K'hinsee, vol. 8, #3, 1961, pp.250 259.

CHARLES B. PARKER, Primary Examiner. LEWIS GOT'TS, IRVING MARCUS, Examine1-s. 

1. A COMPOUND OF THE FORMULA 